Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) cause substantial morbidity among aging men;however, the factors leading to the development and progression of BPH/LUTS remain poorly understood, possibly because BPH/LUTS is a highly heterogenous condition. Animal and human cell culture data suggest that the autonomic nervous system may play an important role in BPH/LUTS. Additionally, alpha-adrenergic receptor inhibitors have emerged as a useful pharmacologic treatment for BPH, suggesting that the autonomic nervous system may contribute to development and/or progression of BPH. We therefore hypothesize that men who have higher levels of autonomic nervous system tone also have a higher likelihood of developing BPH, and propose a transdisciplinary study to examine associations between genetic, physiologic, and serum surrogate measures of autonomic nervous system function and BPH outcomes. To accomplish this study, we will take advantage of data available through an established, population-based cohort of men residing in Olmsted County, MN for whom detailed, long-term urologic outcome and risk factor information is available. We will genotype polymorphisms in genes related to autonomic nervous system function using DNA samples from 585 men in this population and determine whether specific polymorphisms are associated with development of BPH outcomes. Second, we will recruit men with severe LUTS and men without LUTS to participate in a one-hour screen of autonomic function, and will determine whether physiologic and serum measures of autonomic function are associated with presence of BPH measures. Through completion of this study, we will provide insight into the association between the autonomic nervous system and specific components of BPH/LUTS. This study will help us begin to partition out the underlying etiologies that lead to the development and progression of this heterogeneous condition, and begin to identify factors related to prevention and treatment of this common syndrome. PUBLIC HEALTH RELEVANCE: Nearly one-fourth to one-half of aging men will experience BPH and associated LUTS. This study will use state-of-the-art techniques to understand how the autonomic nervous system might contribute to development of BPH/LUTS. Results from this study may assist with treatment and prevention of this syndrome.